2. Signaling Pathways
  3. Apoptosis
  4. Necroptosis

Necroptosis

Necroptosis is a form of regulated necrotic cell death mediated by receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) and generally manifests with morphological features of necrosis. Necroptosis is characterized by early loss of plasma membrane integrity, leakage of intracellular contents, and organelle swelling. The cells dying through necroptosis lack the typical apoptotic characteristics, such as membrane blebbing, chromatin condensation, and intranucleosomal DNA cleavage into 180 bp DNA laddering, but may show TUNEL positivity.

Necroptosis triggers innate immune responses by rupturing dead cells and releasing intracellular components, it can be caused by Toll-like receptor (TLR)-3 and TLR-4 agonists, tumor necrosis factor (TNF), certain microbial infections, and T cell receptors. Necroptosis signaling is modulated by receptor-interacting protein kinase (RIPK) 1 when the activity of caspase-8 becomes compromised. Activated death receptors (DRs) cause the activation of receptor-interacting serine-threonine kinase 1 (RIPK1) and the RIPK1 kinase activity-dependent formation of an RIPK1-RIPK3-MLKL, which is complex II. RIPK3 phosphorylates MLKL, ultimately leading to necrosis through plasma membrane disruption and cell lysis.

Necroptosis Related Products (130):

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-W010800R
    Cholesteryl hemisuccinate (Standard)
    		Inhibitor
    Cholesteryl hemisuccinate (Standard) is the analytical standard of Cholesteryl hemisuccinate. This product is intended for research and analytical applications. Cholesteryl hemisuccinate is a with hepatoprotective an anticancer activity. Cholesteryl hemisuccinate inhibits Acetaminophen (AAP, HY-66005) hepatotoxicity, and prevents AAP-induced hepatic apoptosis and necrosis. Cholesteryl hemisuccinate inhibits DNA polymerase and DNA topoisomerase to inhibit DNA replication and repair and cell division. Thus, Cholesteryl hemisuccinate inhibits tumor growth[1][2].
    Cholesteryl hemisuccinate (Standard)
  • HY-B0339S
    Primidone-d5
    		Inhibitor 99.00%
    Primidone-d5 is the deuterium labeled Primidone. Primidone is the orally active inhibitor for TRPM3 (IC50 = 0.6 μM), RIP kinase and voltage-gated sodium channel, and the antagonist for GABA receptor. Primidone can be used as the analgesic and anticonvulsant agent.
    Primidone-d<sub>5</sub>
  • HY-173185
    RIP1-IN-1
    		Inhibitor
    RIP1-IN-1 is an orally active RIP1 inhibitor with strong RIP1 binding affinity (Kd: 110 nM). RIP1-IN-1 exhibits strong anti-necroptosis activity. RIP1-IN-1 effectively inhibits the formation of necrosomes by blocking the phosphorylation of RIP1, RIP3 and MLKL signaling pathways. RIP1-IN-1 inhibits necroptosis and can be used in the study of acute liver injury.
    RIP1-IN-1
  • HY-156087G
    Cholicamideβ (GMP)
    		Inducer
    Cholicamideβ (GMP) is a GMP grade of Cholicamideβ. Cholicamideβ (compound 6) is a self-assembling, small molecule, cancer vaccine adjuvant. Cholicamideβ can form virus-like particles with low cytotoxicity. Cholicamideβ, upon binding to peptide antigens, enhances antigen presentation by dendritic cells and induces antigen-specific T cells. Cholicamideβ can induce apoptosis and necrosis.
    Cholicamideβ (GMP)
  • HY-169509
    Topoisomerase I/II inhibitor 8
    		Inducer
    Topoisomerase I/II Inhibitor 8 (Compound Ru7) is a dual catalytic inhibitor of Topoisomerase I/II, capable of inducing DNA damage and PARP-1 activation, which subsequently leads to the activation of RIPK1, RIPK3, and MLKL, ultimately triggering necroptosis. Topoisomerase I/II Inhibitor 8 demonstrates remarkable anticancer activity by effectively targeting the nuclei of cancer cells and inducing cell death through necroptosis, showing great clinical potential in circumventing drug resistance in cancer treatment.
    Topoisomerase I/II inhibitor 8
  • HY-153435
    RIP1 kinase inhibitor 5
    		Inhibitor
    RIP1 kinase inhibitor 5 (example 1) is a potent inhibitor of RIP1, which is used as a checkpoint kinase to control tumor immunity. RIP1 kinase inhibitor 5 is similar with SIR1-365 (compound 13), which inhibits necrosis and iron death activity.
    RIP1 kinase inhibitor 5
  • HY-149407
    Multi-kinase-IN-4
    		Activator
    Multi-kinase-IN-4 (compound 5d) is multi-targeted kinase inhibitor, including VEGFR2, EGFR, HER2, and CDK2, with IC50 values of 0.33, 0.22, 0.18 and 2.09 μM, respectively. Multi-kinase-IN-4 shows broad-spectrum anti-cancer activities against HepG2, MCF-7, MDA-231, and HeLa cell lines (IC50 = 1.94–7.1 µM), but exhibits lower toxicity in the WI-38 cells (IC50 = 40.85 µM). Multi-kinase-IN-4 induces apoptosis and arrests cell cycle at S phase in HepG2 cells. Multi-kinase-IN-4 has the potential for the research of cancer.
    Multi-kinase-IN-4
  • HY-162097
    RIPK1-IN-20
    		Inhibitor
    RIPK1-IN-20 (compound 13c) has a favorable RIPK1 kinase inhibition activity with an IC50 value of 59.8 nM. RIPK1-IN-20 blocks TNFα-induced necroptosis in both human and murine cells (EC50=1.06–4.58 nM).
    RIPK1-IN-20
  • HY-172909
    RIPK3-IN-5
    		Inhibitor
    RIPK3-IN-5 (compound 32) is a potent RIPK3 inhibitor with an IC50 of 27 nM. RIPK3-IN-5 also inhibits necroptosis with an EC50 of 0.45 μM.
    RIPK3-IN-5
  • HY-178464
    RIPK1-IN-34
    		Inhibitor
    RIPK1-IN-34 is a selective, brain-penetrant RIPK1 inhibitor (IC50 = 126.70 nM) with almost no inhibitory effect on RIPK3 (IC50 ＞ 10, 000 nM). RIPK1-IN-34 offers substantial neuroprotection by inhibiting the phosphorylation of RIPK1, RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) within the necroptosis pathway. RIPK1-IN-34 shows the neuroprotective effect in a rat middle cerebral artery occlusion (MCAO) model. RIPK1-IN-34 can be used for the study of anti-acute ischemic stroke (AIS).
    RIPK1-IN-34
  • HY-175030
    TNI-97
    		Inducer
    TNI-97 is a selective and orally active HDAC6 inhibitor, with an IC50 of 0.2 nM. TNI-97 potently inhibited TNBC cell MDA-MB-453 growth and clonogenicity. TNI-97 induces PANoptosis including apoptosis, necroptosis and pyroptosis in MDA-MB-453 cells. TNI-97 shows antitumor activity in the mice carrying the MDA-MB-453 xenograft or carrying murine-derived TNBC cell allografts. TNI-97 can be used for the study of triple-negative breast cancer.
    TNI-97
  • HY-B1984S
    p,p'-DDD-d8
    		Inducer
    p,p'-DDD-d8 is the deuterium labeled p,p'-DDD[1]. p,p'-DDD (4,4’-DDD) is an organochlorine insecticide, a major metabolite of p,p'-DDT. p,p'-DDD is an agonist at estrogen receptor α(ERα) and ERβ. p,p'-DDD increases DNA damage, apoptosis and necrosis in peripheral blood. p,p'-DDD stimulates cell proliferation in SKBR3 cells. p,p'-DDD activates the AP-1 transcription factor. p,p'-DDD decreases sleep times of barbiturates and steroids in rats.
    p,p'-DDD-d<sub>8</sub>
  • HY-B0863S5
    Glyphosate-13C,15N-1
    Glyphosate-13C,15N-1 is the 13C- and 15N-labeled Glyphosate (HY-B0863). Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is an herbicidal derivative of the amino acid glycine. Glyphosate inhibits the enzymatic activity of the 5-endopyruvylshikimate 3-phosphate synthase (EPSPS) in the shikimic acid pathway, preventing the synthesis of the aromatic amino acids tyrosine, phenylalanine, and tryptophan. Glyphosate induces oxidative stress, neuroinflammation, and mitochondrial dysfunction, processes that lead to neuronal death by autophagia, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders.
    Glyphosate-<sup>13</sup>C,<sup>15</sup>N-1
  • HY-144277
    RIPK1-IN-12
    		Inhibitor
    RIPK1-IN-12 is a potent RIPK1 inhibitor. RIPK1-IN-12 inhibits necroptosis in both human and mouse cells, with EC50 values of 1.6 and 2.9 nM, respectively.
    RIPK1-IN-12
  • HY-160170
    Necrosis inhibitor 3
    		Inhibitor
    Necrosis inhibitor 3 (compound B3) is a poteng inhibitor of necrosis, with the IC50 value of 0.29 nM in HT29 cells.
    Necrosis inhibitor 3
  • HY-116107
    AG311
    		Inducer
    AG311 is an anticancer and antimetastatic agent. AG311 induces rapid necrosis in numerous cancer cell lines.
    AG311
  • HY-156920
    VDX-111
    		Inducer
    VDX-111 is an analog of vitamin D. VDX-111 exhibits cytotoxicity in ovarian cancer cells through upregulation of RIPK1/RIPK3 pathway and induction of necroptosis. VDX-111 promotes expressions of cytokines and exhibits antitumor activity in mouse model.
    VDX-111
  • HY-155804
    RIP1 kinase inhibitor 8
    		Inhibitor
    RIP1 kinase inhibitor 8 (Compound 77) is a potent and highly selective dihydropyrazole (DHP) RIP1 kinase inhibitor with an IC50 of 20 nM. RIP1 kinase inhibitor 8 prevents necrotic cell death. RIP1 kinase inhibitor 8 shows a favorable pharmacokinetic profile in multiple species.
    RIP1 kinase inhibitor 8
  • HY-156087
    Cholicamideβ
    		Inducer
    Cholicamideβ (GMP) is a GMP grade of Cholicamideβ. Cholicamideβ (compound 6) is a self-assembling, small molecule, cancer vaccine adjuvant. Cholicamideβ can form virus-like particles with low cytotoxicity. Cholicamideβ, upon binding to peptide antigens, enhances antigen presentation by dendritic cells and induces antigen-specific T cells. Cholicamideβ can induce apoptosis and necrosis.
    Cholicamideβ
  • HY-160169
    Necrosis inhibitor 2
    		Inhibitor
    Necrosis inhibitor 2 (Compound B19) is a cell necrosis inhibitor. Necrosis inhibitor 2 can be used to study diseases related to the necrosis pathway, including inflammation, tumors, metabolic diseases and neurodegenerative diseases.
    Necrosis inhibitor 2